HIV and drug abuse is concentrated within the criminal justice system (CJS) resulting in 26% of all HIV+ prisoners nationally being released to the community annually. Therefore, the CJS is an important place to target and empirically test interventions that address the Seek, Test, Treat and Retain (STTR) strategy to reduce HIV transmission within the community. STTR requires that HIV is maximally suppressed, resulting in decreased infectiousness; HIV+ prisoners successfully achieve maximal suppression during incarceration. Three 3 months post-release, however, viral suppression is lost mostly as a consequence of relapse to opioids - opioid dependence (OD) is present in 50% of HIV+ prisoners nationally and 70-85% in the Northeast. Opioid relapse is associated with decreased HAART adherence, discontinuation of HAART and increased HIV risk behaviors in the setting of viral replication - the perfect storm for HIV transmission. Effectively treating OD interrupts this relationship and has great potential to improve HIV outcomes; our team has confirmed this benefit using buprenorphine. Opioid substitution therapy, especially methadone, has had limited uptake within the CJS due to philosophical, safety, regulatory and staffing concerns. Therefore, strategies examining the efficacy of naltrexone (NTX), an opioid antagonist, to improve adherence and retention in care, has great appeal to benefit the individual, but also to reduce HIV transmission within the community. Our specific aim is to conduct a placebo-controlled RCT of depot NTX (d-NTX) for HIV+ prisoners with OD who are transitioning to the community. The placebo-control methodology further strengthens any findings that should be demonstrated. HIV treatment (HIV-1 RNA levels, CD4 count, ART adherence, retention in care), substance abuse (time to relapse to opioid use, % opioid negative urines, opioid craving), adverse side effects and HIV risk behavior (sexual and drug-related risks) outcomes will be compared in 150 subjects within CJS in New Haven, Hartford and Springfield. Subjects will be randomized 2:1 to d-NTX or d-placebo for 6 months and observed for 12 months. This therapeutic approach has great appeal by the CJS, given the ease of monthly injections, lack of diversion, few side effects and no antagonistic philosophical concerns about its use. The strength of this proposal is the team of researchers experienced in HIV, addiction and the CJS, the novel use of treating OD as a means to improve HIV outcomes, over 20 years of conducting research in the CJS and the novelty of using d-NTX for the treatment of OD. If this placebo-controlled trial of d-NTX among released HIV+ CJS-involved persons with OD demonstrates efficacy and safety, it is likely to become an evidence-based intervention to intervene with released HIV+ prisoners. As such, the individual, our health care system and society have a high likelihood to benefit - especially on the reduction of HIV within the community.